血管性痴呆小鼠空间工作记忆障碍的机制探讨

Mechanisms of spatial memory impairment in mice with vascular dementia

背景血管性痴呆(vascular dementia,VaD)是继阿尔茨海默病之后最常见的痴呆原因之一,主要表现为认知功能障碍,其发病机制尚不完全清楚。目的探讨VaD小鼠空间工作记忆障碍的发病机制。方法16只ICR小鼠随机分为对照组和VaD组,VaD组小鼠以左侧颈总动脉夹闭再灌注方法建立VaD模型。术后应用Longa评分法和平衡木行走实验对小鼠进行神经性评价,通过T迷宫对小鼠的工作记忆行为学进行分析,氯化三苯基四氮唑(2,3,5-triphenyltetrazolium chloride,TTC)染色法评价小鼠的脑梗死体积,应用蛋白免疫印迹法对海马蛋白N-甲基-D-天冬氨酸受体2A(N-methyl-D-aspartate receptors 2A,NMDAR2A)表达量进行检测。结果与对照组小鼠相比,VaD组小鼠神经功能评分降低,T迷宫的工作记忆行为学正确率下降,工作记忆任务的完成时间延长,脑梗死体积增大,海马NMDAR2A蛋白表达水平降低(P<0.05)。结论VaD小鼠的空间工作记忆受损,可能与海马NMDAR2A表达量降低有关。

Background Vascular dementia(VaD)with cognitive impairment is the second most common type of dementia,mainly manifests as cognitive dysfunction,and its pathogenesis is still unclear.Objective To explore the underlying pathogenesis mechanisms of spatial working memory impairment in mice with VaD.Methods Sixteen ICR mice were randomly divided into the control group and the VaD group.The left common carotid artery was clamped and reperfused in the VaD group to establish the VaD model.After operation,the Longa scoring method and the balance beam experiment were used to evaluate the neurological score,and the spatial working memory behavior was tested with T maze.The 2,3,5-triphenyltetrazolium chloride(TTC)staining method was used to evaluate the cerebral infarct volume of mice,and the expression of N-methyl-D-aspartate receptors 2A(NMDAR2A)in hippocampus was detected by western blot.Results Compared with the control group,the neurological function scores were lower,the accuracy of working memory in T maze decreased,the completion time of working memory tasks prolonged,the cerebral infarction volume increased,and the expression level of NMDAR2A in hippocampus decreased in the VaD group(P<0.05).Conclusion The impairment of spatial working memory abilities in VaD rats maybe related to the decreased expression level of NMDAR2A in hippocampus.